Cervical Intraepithelial Neoplasia Grade Research Articles

Nationwide cohort study on the risk of high-grade cervical dysplasia and carcinoma after conservative treatment or hysterectomy for adenocarcinoma in situ.

Internationally, little consensus exists about the best treatment for cervical adenocarcinoma in situ (AIS). This study aimed to determine the incidence of recurrent high-grade cervical dysplasia and development of local cervical cancer after treatment for AIS. This nationwide, retrospective cohort study included patients with AIS, who were treated by a large loop excision of the transformation zone (LLETZ), cold-knife conization (CKC), or hysterectomy between January 1, 1990 and December 31, 2021 in the Netherlands. Pathology reports were retrieved from the Dutch Nationwide Pathology Databank (Palga). Primary outcomes were the cumulative incidences of high-grade cervical dysplasia (cervical intraepithelial neoplasia grade 2 or 3, and AIS) and local cervical cancer up to 20 years after primary treatment. In total, 4243 patients with AIS were included. The primary treatment was a LLETZ, CKC, or hysterectomy in 1593, 2118, and 532 patients, respectively. The incidence of recurrent high-grade cervical dysplasia after LLETZ (10.5%; 95%CI: 8.6-12.3) was higher than after CKC (5.5%; 95%CI: 4.4-6.6, p <.0001). When a radical excision, that is, surgical margins free of dysplasia at end of treatment, was achieved, the incidence of recurrent high-grade dysplasia and local cervical cancer did not differ between LLETZ (5.6% [95%CI: 3.3-7.9] and 1.9% [95%CI: 0-4.4]) and CKC (4.7% [95%CI: 3.5-5.8], p = .631 and 1.5% [95%CI: 0.7-2.3], p = .918). After hysterectomy, none of the patients developed cervical dysplasia or local cervical cancer. Conservative treatment for AIS can be considered a safe and final treatment modality when a radical excision is achieved.

Post-marketing study design to evaluate the effectiveness of the 9-valent and 4-valent HPV vaccines on serious HPV-related cervical disease in China.

The 4-valent (4 v) and 9-valent (9 v) human papillomavirus (HPV) vaccines are approved in China for females aged 9-45 years. However, the real-world impact of 4vHPV or 9vHPV vaccination for the prevention of high-grade cervical disease in Chinese women is lacking. Two post-marketing surveillance studies will be conducted to measure the occurrence of high-grade cervical lesions in Chinese women who had received ≥1 dose of the 4vHPV (aged 20-45 years) or 9vHPV (aged 16-26 years) vaccine in Ningbo, China. Vaccination data will be extracted from the Ningbo Regional Health Information Platform (NRHIP) from the date of the first 4vHPV (January 9, 2018) or the first 9vHPV (January 25, 2019) vaccination to March 31, 2021. The primary 4vHPV and 9vHPV vaccinated cohorts will include women vaccinated per protocol. The 4vHPV/9vHPV vaccinated test-negative (cervical HPV negative; ThinPrep cytology test negative) and corresponding matched unvaccinated HPV test-negative sub-cohorts will also be assessed. Outcomes will be the occurrence of new-onset cervical intraepithelial neoplasia grade 2/3, adenocarcinoma in situ, and invasive cervical cancer. This study aims to demonstrate that such a methodological approach is feasible and can be used to assess the impact of HPV vaccination in other regions across China.

Research Progress of Immune Mechanisms Related to Persistent HPV Infection in CIN after Cervical Conization

Persistent human papillomavirus (HPV) infection is associated with the grading of cervicalintraepithelial neoplasia (CIN), high-risk HPV infection, multiple HPV infections, high HPV load,HPV infection of surgical margin, and age in CIN after conization. The immune mechanism iscomplex and is primarily related to vaginal microecology disorders, immune escape, immuneresponse impairment, and the release of regulatory cytokines. Currently, the treatment methods forpostoperative persistent HPV infection include surgical treatment, antiviral treatment, vaccination,and other approaches.

Nationwide study on development and validation of a risk prediction model for CIN3+ and cervical cancer in Estonia

Transitioning to an individualized risk-based approach can significantly enhance cervical cancer screening programs. We aimed to derive and internally validate a prediction model for assessing the risk of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) and cancer in women eligible for screening. This retrospective study utilized data from the Estonian electronic health records, including 517,884 women from the health insurance database and linked health registries. We employed Cox proportional hazard regression, incorporating reproductive and medical history variables (14 covariates), and utilized the least absolute shrinkage and selection operator (LASSO) for variable selection. A 10-fold cross-validation for internal validation of the model was used. The main outcomes were the performance of discrimination and calibration. Over the 8-year follow-up, we identified 1326 women with cervical cancer and 5929 with CIN3+, with absolute risks of 0.3% and 1.1%, respectively. The prediction model for CIN3 + and cervical cancer had good discriminative power and was well calibrated Harrell’s C of 0.74 (0.73–0.74) (calibration slope 1.00 (0.97–1.02) and 0.67 (0.66–0.69) (calibration slope 0.92 (0.84–1.00) respectively. A developed model based on nationwide electronic health data showed potential utility for risk stratification to supplement screening efforts. This work was supported through grants number PRG2218 from the Estonian Research Council, and EMP416 from the EEA (European Economic Area) and Norway Grants.

The Level of Serum Selenium in Patients with Cervical Intraepithelial Neoplasia in Medical City/ Baghdad Teaching Hospital

Introduction: Selenium is an essential trace element involved in different physiological functions of the human body. An inverse relationship between serum selenium levels and cervical intraepithelial neoplasia has been reported. cervical intraepithelial neoplasia is regarded as a potentially premalignant transformation of squamous cells of the cervix. Objectives: To evaluate the relationship between the serum level of selenium and cervical intraepithelial neoplasia. Methods: A case-control study was conducted at Baghdad Teaching Hospital and Iraqi National Cancer Research Center in the University of Baghdad during the period from July 2021 to July 2022. A convenient sample of 100 women was enrolled in the current study and included case group which consisted of 50 women who were diagnosed with cervical intraepithelial neoplasia and control group which consisted of 50 women who did not have cervical intraepithelial neoplasia as confirmed through histological examination after punch biopsy by colposcopy. Results: The serum level of the selenium was significantly lower in the case groups compared to the control groups (P-value=0.001). In addition, the proportion of the participant with abnormal levels of selenium was significantly higher in the case group compared to the control group (P-value=0.001). In the case group, there was a significant difference between the cervical intraepithelial neoplasia grade regarding the serum level of selenium, the level of selenium significantly decreased with the progression of the disease (P-value=0.001). Conclusions: Selenium deficiency may significantly increase the incidence of cervical intraepithelial neoplasia. In addition, it significantly impacts the transformation to a higher degree as there was a significant difference between cervical intraepithelial neoplasia I, II, and III regarding the level of serum selenium.

Age-specific 3-year risk of cervical precancer among HPV-positive women attending screening: a post hoc analysis from a retrospective cohort

This post hoc analysis explored the age-specific risk of cervical precancer in women infected with human papillomavirus (HPV), using data from a cohort of 7263 participants aged 21-71years undergoing cervical screening. We found a slightly varied prevalence of high-risk HPV (hrHPV) in different age, with highest in women under 30 years old (9.28% for 13 hrHPVs tested by HC2-HPV, 10.82% for 14 hrHPVs tested by DH3-HPV). However, the prevalence of cytology abnormalities peaked in age 30–39 years (~ 3.6%). A total of 5840 women completed 3-year follow-up. Among them, 558 were positive for HC2 assay and 583 were positive for DH3-HPV at baseline. Of note, the 3-year cumulative risks for cervical intraepithelial neoplasia grade 2+ (CIN2+) or grade 3+ (CIN3+) in women infected with high-risk HPV did not increase with age but declined (e.g., 41.67%, 27.78%, 26.42%, 15.98%, and 18% for CIN2 + risk in HC2-positive women at year 25–29, year 30–39, year 40–49, year 50–59, and year 60–71, respectively). If stratified by the median age, younger women (25–48 years) positive with HC2-HPV at baseline had a higher 3-year CIN2+/CIN3 + risk than older women (49–71 years) [26.55% (95%CI = 21.8-31.92%) vs. 18.28% (95%CI = 14.11-23.34%), P = 0.019; 15.52% (95%CI = 11.81-20.14%) vs. 9.7% (95%CI = 6.71-13.83%), P = 0.039]. Similarly, for women positive with DH3-HPV at baseline, younger group had a higher 3-year CIN2+/CIN3 + risk than older group [26.44% (95%CI = 21.73-31.75%) vs. 17.01% (95%CI = 13.11-21.78%), P = 0.006; 15.25% (95%CI = 11.6-19.8%) vs. 9.03% (95%CI = 6.24-12.9%), P = 0.021]. These findings indicate the potential value of age-specific risk assessment in cervical cancer screening.

Comparative study of triage strategies for women with atypical squamous cells of undetermined significance in the post-vaccine era.

The research focused on a comparative analysis of triage strategies for women with Atypical Squamous Cells of Undetermined Significance (ASC-US) before and after receiving the HPV vaccine, aiming to optimize cervical cancer prevention strategies, especially in resource-limited healthcare settings. Between September 2018 and December 2023, 7,511 women aged 21 years or older who underwent liquid-based cytology for cervical cancer screening were recruited. Women diagnosed with ASC-US were included in the study. All participants underwent HPV testing and liquid-based cytology examination, and those with abnormal results were referred for colposcopy. Women with abnormal colposcopy findings underwent further histopathological examination. The gold standard for diagnosis was pathological, with cervical intraepithelial neoplasia grade 2 or higher (CIN2+) on histology as the endpoints. In the final analysis, 933 women with ASC-US were enrolled as the unvaccinated group, with 179 of them testing positive for HPV 16/18. Assuming that all women would receive the bivalent vaccine targeting HPV 16/18 in the post-vaccine era, and given that the vaccine protection rate is 100% against HPV 16/18, then 754 women excluding those of HPV 16/18 positive would comprise the vaccinated group. In the unvaccinated group, the overall HPV positivity rate was 59.27% among ASC-US women, with a 100% HPV prevalence rate among those with CIN2+ lesions. The combination genotyping model of HPV16/18 showed the highest specificity (81.77%) and the lowest referral rate (32.37%). In the vaccinated group, the HPV positivity rate was 49.61% among ASC-US women, with a 100% HPV prevalence rate among those with CIN2+ lesions. The specificity of HPV33/58 was the highest (86.99%), and the colposcopy referral rate was lowest (27.54%), with statistical significance. Sensitivity, positive predictive value, and negative predictive value were not statistically significant. HPV16/18 demonstrated a more efficacious triaging effect in the unvaccinated group. HPV33/58 will potentially replace HPV16/18 as the priority screening genotyping among vaccinated populations.

Cost-Effectiveness of Computer-Assisted Cytology in a Primary hrHPV-Based Cervical Cancer Screening Programme.

Computer-assisted screening (CAS) shows equal performance compared to manual screening, although results are heterogeneous. Furthermore, using CAS may save costs through a potentially increased screening productivity of technicians, therefore also offering a solution for temporary and structural capacity shortage. We evaluated the circumstances under which CAS will be cost-effective compared to manual cytology triage in a primary HPV-based cervical screening programme. Microsimulation model MISCAN-Cervix was used to evaluate 198 different CAS scenarios with varying probabilities to detect cervical intraepithelial neoplasia grade 1 (CIN1) and CIN3 and cost reductions per test, compared to manual cytology triage. Cost-effectiveness was evaluated by costs per (quality-adjusted) life year ((QA)LY) gained. CAS will be cost-effective in all scenarios, except for the following combinations: (1) no cost reduction and an increased probability of detecting CIN1, (2) a cost reduction of €2 per test and an increased probability of detecting CIN1 from 4% onwards or (3) a cost reduction of €4 per test and an increased probability of detecting CIN1 from 6% onwards, compared to manual cytology triage. All CAS scenarios with any reduction in the probability of detecting CIN1 (i.e., increased CIN2+ specificity), or a reduction in costs from €6 per test onwards suggested a more cost-effective strategy compared to manual cytology triage. As we based our analysis on a realistic range in costs and test performance, the implementation of CAS is likely to be cost-effective. Our results can be used as a guideline to advise when to choose CAS instead of manual cytology triage.

Human papillomavirus self-sampling and urine-sampling tests and the management and short-term outcomes of cervical intraepithelial neoplasia: A prospective observational study.

The importance of human papillomavirus (HPV) co-testing using physician-, self-, and urine-collected samples to predict cervical intraepithelial neoplasia (CIN) grade 1-2 prognoses has not been previously reported. Therefore, this study aimed to investigate outcomes of patients with CIN 1-2 who simultaneously underwent physician-, self-, and urine-collection sampling tests. This study was conducted in Japan between October 2019 and November 2022 and examined the proportion of cases with CIN 1-2 progressions, the percentage of cases with persistent CIN 1-2, and the outcome differences according to the results of physician-, self-, and urine-sampling tests. There were 105 and 59 CIN 1 and 2 cases, respectively, with progression or persistence in 27 (29.3%) and 21 (50.0%) cases, respectively. The median follow-up was 20 and 12 months, respectively. Progression and persistence of CIN 1 were significantly associated with HPV-positive physician- and self-collected samples. No significant difference was observed between cases with CIN 2 who had HPV-positive and HPV-negative results using any sampling method. Physician- and self-testing for HPV are crucial for predicting disease progression risk in CIN 1 cases. Future research with an extended observation period and consideration of the progression risks is warranted.

Ranking the attribution of high-risk genotypes among women with cervical precancers and cancers: a cross-sectional study in Ningbo, China

BackgroundThe region-specific importance of carcinogenic HPV genotypes is required for optimizing HPV-based screening and promoting appropriate multivalent HPV prophylactic vaccines. This information is lacking for Ningbo, one of the first cities of China’s Healthy City Innovation Pilot Program for Cervical Cancer Elimination. Here, we investigated high-risk HPV (HR-HPV) genotype-specific distribution and attribution to biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) before mass vaccination in Ningbo, China.MethodsA total of 1393 eligible CIN2+ archived blocks (including 161 CIN2, 1107 CIN3, and 125 invasive cervical cancers [ICC]) were collected from 2017 to 2020 in Ningbo. HR-HPV DNA was genotyped using the SPF10-DEIA-LiPA25 version 1 detection system and the SureX HPV 25X Genotyping Kit. Genotype-specific attribution to CIN2+ was estimated using a fractional contribution approach.ResultsRanking by the attributable proportions, HPV16 remained the most important genotype in both cervical precancers and cancers, accounting for 36.8% of CIN2, 53.2% of CIN3, and 73.3% of ICC cases. Among cervical precancers, HPV52 (17.3% in CIN2, 12.7% in CIN3) and HPV58 (13.9%, 14.9%) ranked second and third, while HPV33 (8.3%, 7.9%) and HPV31 (6.5%, 4.1%) ranked fourth and fifth, respectively. However, among ICCs, HPV18 (5.7%) accounted for the second highest proportion, followed by HPV33 (5.4%), HPV58 (4.0%), and HPV45 (3.2%). HPV18/45 together accounted for 46.8% of adenocarcinomas, which was slightly lower than that of HPV16 (47.7%). The remaining HR-HPV genotypes (HPV35/39/51/56/59/66/68) combined accounted for only 6.7% of CIN2, 2.9% of CIN3, and 4.2% of ICC.ConclusionsWith Ningbo’s strong medical resources, it will be important to continue HPV16/18 control efforts, and could broaden to HPV31/33/45/52/58 for maximum health benefits. However, different strategies should be proposed for other HR-HPV genotypes based on their lower carcinogenic risks.

Head-to-head comparison of two human papillomavirus vaccines for efficacy against cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ-population-based follow-up of two cluster-randomized trials.

We report head-to-head comparison of the bivalent and quadrivalent HPV vaccine efficacies against immediate precursors of cervical cancer from 15 years' country-wide cancer registry follow-up of phase III trial cohorts and an age-aligned cohort of unvaccinated women. These individually and/or clusterrandomized cohorts of HPV6/11/16/18- and HPV16/18-vaccinated and unvaccinated women were enrolled, respectively, in 2002, 2004, and 2003/2005. The trial cohorts comprised initially 16- to 17-year-old HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866) and HPV16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2,465), and 16,526 initially 16- to 19-year-old unvaccinated controls. After active 4-year clinical follow-up, passive, country-wide Finnish Cancer Registry (FCR) follow-up for cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) was based on consented use of unique personal identifiers and started 6 months after the end of the FUTURE II and PATRICIA trials in 2007 and 2009, and ended at the end of 2019. The follow-up with altogether 229,020 follow-up years was age-aligned to ensure that similarly aged cohorts were passively followed up for 15 years post=vaccination for the intention-to-treat analyses of vaccine efficacy. Overall, we identified 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts, respectively, during the FCR-based follow-up. In the unvaccinated cohort, we identified 281 CIN3 cases, 20 AIS cases, and 13 cases with invasive cervical cancer. Vaccine efficacies against CIN3+ were 68.4% and 64.5% for the quadrivalent and the bivalent vaccines, respectively, with overlapping confidence intervals. Long-term follow-up of randomized, initially adolescent HPV-vaccinated and unvaccinated cohorts shows, in this head-to-head setting, that the bivalent and quadrivalent HPV vaccines are equally effective against immediate precursors of cervical cancer.

Time trends in the clinical management of cervical intraepithelial neoplasia grade 2: A Danish register-based study.

Active surveillance for cervical intraepithelial neoplasia grade 2 (CIN2) has been implemented recently in many countries, including the Nordic countries. In Denmark, the only eligibility criterion for active surveillance for CIN2 is that the woman should be of reproductive age. With this study, we aimed to evaluate clinical and socioeconomic characteristics in women with CIN2 managed by active surveillance or large loop excision of the transformation zone (LLETZ) and to evaluate temporal changes in the clinical management of CIN2. We conducted a Danish nationwide study using data from healthcare registries. All female residents aged 18-40 years, diagnosed with incident CIN2 from January 1, 1998, to February 29, 2020, were included. We collected data on age, index cytology result, year of CIN2 diagnosis, region of residence, civil status, HPV vaccination status, and socioeconomic position indicators. The variables were tabulated overall and by management group (active surveillance vs. LLETZ). To evaluate time trends, we used joinpoint regression to calculate the annual percentage change (APC), including 95% confidence intervals (CI). Of the 27 536 women with CIN2 included, 12 500 (45.4%) underwent active surveillance, and 15 036 (54.6%) underwent a LLETZ. Women undergoing active surveillance were younger, more often HPV-vaccinated, and more likely to have a normal/low-grade index cytology result than women undergoing LLETZ. Socioeconomic position indicators did not differ. Over time, the proportion of women undergoing active surveillance increased from 21.7% in 2004 to 73.6% in 2019 (APC 9.7, 95% CI 8.1-11.4). The proportion of women undergoing active surveillance aged <30 declined over time (APC -2.2, 95% CI -2.9 to -1.5). The proportion of women with normal/low-grade index cytology increased slightly to 51.6% in 2019 (APC 0.8, 95% CI 0.4-1.3). The use of active surveillance for CIN2 has increased over the past two decades in Denmark. Observed differences in characteristics between women undergoing active surveillance vs LLETZ are likely related to indications for clinical management.

Multiscale Optical Imaging Fusion for Cervical Precancer Diagnosis: Integrating Widefield Colposcopy and High-Resolution Endomicroscopy.

Early detection and treatment of cervical precancers can prevent disease progression. However, in low-resource communities with a high incidence of cervical cancer, high equipment costs and a shortage of specialists hinder preventative strategies. This manuscript presents a low-cost multiscale in vivo optical imaging system coupled with a computer-aided diagnostic system that could enable accurate, real-time diagnosis of high-grade cervical precancers. The system combines portable colposcopy and high-resolution endomicroscopy (HRME) to acquire spatially registered widefield and microscopy videos. A multiscale imaging fusion network (MSFN) was developed to identify cervical intraepithelial neoplasia grade 2 or more severe (CIN 2+). The MSFN automatically identifies and segments the ectocervix and lesions from colposcopy images, extracts nuclear morphology features from HRME videos, and integrates the colposcopy and HRME information. With a threshold value set to achieve sensitivity equal to clinical impression (0.98 [p = 1.0]), the MSFN achieved a significantly higher specificity than clinical impression (0.75 vs. 0.43, p = 0.000006). Our findings show that multiscale optical imaging of the cervix allows the highly sensitive and specific detection of high-grade precancers. The multiscale imaging system and MSFN could facilitate the accurate, real-time diagnosis of cervical precancers in low-resource settings.

Triage performance of PAX1m/JAM3m in opportunistic cervical cancer screening of non‒16/18 human papillomavirus-positive women: a multicenter prospective study in China

ObjectivesIn this study, we aimed to validate the performance of the PAX1 and JAM3 methylation (PAX1m/JAM3m) test as a triage tool for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3 +) in non-16/18 high-risk human papillomavirus-positive patients (non-16/18 hrHPV +).MethodsThe triage performance of liquid-based cytology (LBC) and the PAX1m/JAM3m test for detecting CIN3 + were compared.ResultsIn total, 1851 participants had cervical histological outcomes and were included in the analysis. The sensitivity/specificity of the LBC test results with atypical squamous cells of undetermined significance or worse (LBC ≥ ASCUS) and the PAX1m/JAM3m test were 90.1%/26.7% and 84.8%/88.5%, respectively. PAX1m/JAM3m( +) had the highest diagnostic AUC (0.866, 95% confidence interval (CI) 0.837–0.896) in the whole cohort. All cancers (n = 20) were detected by PAX1m/JAM3m(+). Compared with LBC ≥ ASCUS, PAX1m/JAM3m(+) reduced the number of patients who needed referral for colposcopy by 57.21% (74.66% vs. 17.45%). The odds ratios for detecting CIN3 + by LBC ≥ ASCUS and PAX1m/JAM3m(+) were 3.3 (95% CI 2.0–5.9) and 42.6 (27.1–69.6), respectively (p < 0.001). The combination of LBC ≥ ASCUS or PAX1m/JAM3m(+) slightly increased the diagnostic sensitivity (98.0%, 95% CI: 95.8–100%) and referral rate (77.09%) but reduced the diagnostic specificity (24.8%, 22.7–26.8%).ConclusionsIn non-16/18 hrHPV(+) women, PAX1m/JAM3m was superior to cytology for detecting CIN3 + . Compared with LBC ≥ ASCUS, PAX1m/JAM3m(+) reduced the number of significant referrals to colposcopy without compromising diagnostic sensitivity.

Association between folate level and cervical intraepithelial neoplasia risk: a systematic review and meta-analysis.

There were several studies about the association between folate level and the risk of cervical intraepithelial neoplasia (CIN). This meta-analysis was conducted to evaluate whether folate deficiency is related to a high risk of CIN and cervical cancer. Odds ratios (ORs)/relative risks and 95% confidence intervals (CIs) were summarized regarding the association between folate level and risk of CIN or cervical cancer. The meta-analysis indicated that higher serum folate levels (the second, third, and fourth quartiles of serum folate) were associated with a lower risk of CIN, as demonstrated by a random-effects model (OR = 0.42, 95% CI: 0.28-0.62). Conversely, no significant association was found between erythrocyte folate levels and the risk of CIN, as indicated by a random-effects model (OR = 0.69, 95% CI: 0.43-1.12). In addition, random-effects models demonstrated that higher serum folate levels (the second, third, and fourth quartiles of serum folate) were associated with lower risks of CIN grade 1 and CIN grades 2 or 3, compared with the lowest quartile of serum folate (CIN grade 1: OR = 0.52, 95% CI: 0.29-0.93; CIN grades 2 or 3: OR = 0.33, 95% CI: 0.19-0.58). Higher serum folate levels (the second, third, and fourth quartiles of serum folate) were associated with a lower risk of cervical cancer, compared with the lowest quartile of serum folate (OR = 0.53, 95% CI: 0.36-0.79). Serum low folate levels could increase the risk of CIN and cervical cancer, while erythrocyte folate concentration was not associated with the risk of CIN.

Promise and Perils of Primary HPV Testing.

Cervical cancer screening has reduced morbidity and mortality in many countries, but efforts to optimize screening modalities and schedules are ongoing. Using data from a randomized trial conducted in British Columbia, Canada, in conjunction with a provincial screening registry, Gottschlich and colleagues demonstrated that the estimated risk for precancerous disease (cervical intraepithelial neoplasia grades 2 or worse) at 8 years following a negative human papillomavirus (HPV) test was similar to the current standard of care (Pap testing after 3 years). The study supports extending screening intervals for those with a negative HPV test beyond currently recommended 5-year intervals. In an ideal world, the resources saved through less frequent routine cervical screening could be redirected to increasing screening uptake and follow-up of abnormalities to improve equity in cervical cancer prevention. However, implementation of extending screening intervals remains less than straightforward in settings with fragmented healthcare systems that lack information systems to support patient call/recall, such as the United States. To achieve the full promise of primary HPV testing, stakeholders at every level must commit to identifying and addressing the diverse spectrum of barriers that undergird existing inequities in care access, appropriately resource implementation strategies, and improve health information systems. See related article by Gottschlich et al., p. 904.

Superficial and Invasive Spread of High-grade Squamous Intraepithelial Lesion and Squamous Cell Carcinoma: A Case Report.

We present a case of extensive spread of high-grade squamous intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia grade 3 (CIN3) with foci of invasive squamous cell carcinoma (SCC) in a premenopausal woman. Superficial spread of CIN3 and cervical SCC to the endometrium and/or fallopian tubes is rare, especially in countries with cervical cancer screening programs. Our case occurred during the COVID-19 pandemic, which may have been a major contributing factor to delayed detection and, consequently extensive spread.

Correlation analysis of human papillomavirus E6/E7 mRNA detection with diagnosis, prognosis and recurrence risk in patients with cervical epithelioma.

Cervical intraepithelial neoplasia (CIN) is an important precursor of cervical cancer. Early detection and treatment can reduce the incidence of cervical cancer. To investigate the detection rate of human papillomavirus (HPV) E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia (CIN) and its relationship with CIN progression and diagnosis. One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected. These patients were graded CIN based on colposcopy and cervical pathology. The positive expression rates of HPV E6/E7 mRNA and HPV [polymerase chain reaction (PCR)-reverse dot crossing] were compared among all groups. Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr. The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis. The diagnostic sensitivity, specificity, and sensitivity of PCR-reverse point hybridization technology for secondary CIN were 70.41%, 70.66%, and 0.714, respectively. Sensitivity and specificity for secondary CIN were 752% and 7853%, respectively, the area under the curve value was 0.789. Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I (P < 0.05). In CIN grade I patients with positive for HPV E6/E7 mRNA, in its orientation to grade CIN patients, in its orientation to grade CIN patients, at 69.2%, compared with patients negative for HPV E6/E7 mRNA (30.8%), significant difference (P < 0.05). HPV E6/E7 mRNA and HPV (PCR-reverse dot hybrid) positive expression have a close relationship with CIN-grade disease progression and is an independent risk factor for high-grade CIN lesions.

Immunohistochemistry staining of Eag1 and p16/Ki-67 can help improve the management of patients with cervical intraepithelial Neoplasia after cold knife conversion

BackgroundImmunohistochemistry (IHC) is widely used in the management of patients with cervical intraepithelial neoplasia (CIN) but still has many limitations in clinical practice. We analyzed the correlation of new biomarkers with the severity of CIN and follow-up outcomes in patients after conization to improve the management of patients with CIN.MethodsIHC staining of Eag1 and p16/Ki-67 was performed on cervical tissue sections from 234 patients with suspected CIN2/3. After a series of follow-ups, including human papillomavirus (HPV) test and thinprep cytologic test (TCT) for 1–2 years, the outcomes were collected. IHC scores of biomarkers and follow-up results were used to analyze the correlation and assess the diagnostic efficiency of biomarkers.ResultsThe IHC staining intensity of Eag1 and p16/Ki-67 was significantly different from that of the CIN1-3 groups (p < 0.05). Eag1 expression scores were significantly different in the distribution between the two follow-up groups (p < 0.001). ROC curves based on the correlations between the follow-up outcomes and the Eag1 scores and IS of p16/ki-67 showed that Eag1 had a greater AUC (0.767 vs. 0.666). Logistic regression analysis of the combination of biomarkers revealed a greater AUC value than any single biomarker.ConclusionsEag1 expression was significantly correlated with CIN grade and follow-up outcomes after conization. IHC staining of combinations of biomarkers of Eag1, p16 and Ki-67 may help us to improve the ability to identify risk groups with abnormal follow-up outcomes after treatment for CIN.

Gynecologic infection rates after ablation treatment for cervical intraepithelial neoplasia grade 2 and higher (CIN2+): Secondary analysis of a non-inferiority randomized trial.

Although concerns have been raised regarding potential infection and morbidity in women undergoing ablation treatment for cervical precancer in low- and middle-income countries (LMIC), there is extremely limited data to substantiate this claim. This is a secondary analysis of a randomized non-inferiority trial (id: NCT03084081) that compares the efficacy and safety of three ablation treatments for biopsy-confirmed cervical intraepithelial neoplasia grade 2 or higher (CIN2+): CO2 gas-based cryotherapy, non-gas cryotherapy, and thermal ablation (TA). Here, we present findings regarding the incidence of sexually transmitted infections (STI) and vaginitis post-treatment. Samples were collected at enrollment and again at 6 weeks post-treatment and assessed for STIs (Chlamydia trachomatis (CT), Neisseria gonorrhea (NG), and Trichomonas vaginalis (TV)) and vaginitis (Bacterial vaginosis (BV) and/or Candida albicans (Candida)). This analysis reflects 864 women with baseline and 6-week follow-up data. None of the ablative treatments put women at increased risk for STIs (CT, NG, TV) or vaginitis (BV, Candida). While most women adhered to post-treatment recommendations (97%) and no difference by treatment arm was observed, the incidence of STIs at follow-up in women that did not adhere with a given recommendation was higher compared to their adherent counterparts. The incidence of gynecologic infection did not increase with any of the ablation treatments from baseline to the six-week follow-up. Non-gas cryotherapy and TA emerge as safe alternatives to gas-based cryotherapy with respect to gynecologic infection rates.